It is known that the actions of neutrophils, eosinophils, monocytes, macrophages, and the like, which are blood cells, are involved in the tissue repair processes such as wound healing, degeneration of tumor and the like. Among these, macrophages play an important role in the tissue repair, such as promotion of wound healing by phagocytosis of dead cells and foreign substances that invaded into the living body and production of growth factors etc., and the like.
Therefore, if migration and accumulation, i.e., mobilization, of blood cells, particularly macrophages, to the targeted diseased part can be performed by some method, promotion of tissue repair is expected. Since macrophages are cells differentiated after mobilization of monocytes present in blood to each tissue, it is also possible to promote tissue repair by accumulating monocytes (non-patent document 1).
As a biological substance capable of mobilizing monocytes and macrophages, 1-stearoyl-lysophosphocholine (C18:0-LysoPC), sphingosine-1-phosphoric acid (S1P) and the like, which belong to one kind of lysophospholipid, have been reported (non-patent documents 2, 3). Since monocytes and macrophages recognize concentration gradients of these substances and have the property of being mobilized to concentrated parts, promotion of tissue repair requires an increase in the local concentration. Also, promotion of tissue repair requires continuous mobilization of monocytes and macrophages. However, C18:0-LysoPC exhibits an effect only in a high concentration condition of 10 μM or more, and side effects such as cytotoxicity and the like may occur under higher concentration conditions. On the other hand, SiP exhibits an effect at a lower concentration than C18:0-LysoPC by acting on SiP receptor 1. However, when the concentration is 100 nM or more, it suppresses mobilization of monocytes and macrophages by acting on SiP receptor 2. As a result, the effective concentration range of SiP is extremely narrow and around 10 nM. Furthermore, when it is administered to a living body, the topical lysophospholipid concentration decreases due to blood flow, in addition to a simple diffusion phenomenon, which necessitates intermittent topical administration to maintain the above-mentioned effective concentration. As a result, the quality of life (QOL) is degraded and the treatment costs increase.